Although radiotherapy is highly effective in relieving bone pain from cancer invasion, the mechanism of pain relief remains unclear. To explore the mechanism of radiotherapy-induced analgesia, we have developed an animal model of bone pain resulting from cancer invasion. Using this animal model system, radiation-induced pain response and pain-related signals in the spinal cord were analyzed. The hind paw model of bone pain from cancer invasion was developed by injecting transplantable hepatocellular carcinoma, IICa-1, into the periosteal membrane of the foot dorsum in C3H/HeJ mice. Bony invasion from HCa-1 cells was confirmed by histopathological examinations. We also measured the development of pain-associated behaviors. In this model, changes in the objective level of pain response after irradiation of the tumor were analyzed. Expression of pain-related host signals in the spinal cord, such as calcitonin gene-related peptide (CGRP), substance P, and c-fos, was investigated with immunohistochemical staining. In the histopathological examinations, bone invasion from HCa-I cells was seen from day 7 and was evident at day 14 after injection. Measurable pain-associated behaviors were developed from day 7. In this model, mice treated with radiotherapy showed decreased objective levels of pain with a higher threshold to graded mechanical stimulation than did control mice from day 3 after irradiation. After irradiation of tumors, significant decreases in the expression of CGRP were shown in the spinal cord, whereas neither substance P nor c-fos showed any alteration. We developed a novel hind paw model of bone pain from cancer invasion that was confirmed by histopathological examination and measurable pain-associated behaviors. Radiotherapy decreased the objective level of pain and the underlying mechanism involved in the alteration of pain-related host signal, CGRP, in the spinal cord.
|Number of pages||8|
|Journal||Annals of the New York Academy of Sciences|
|Publication status||Published - 2004|
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)
- History and Philosophy of Science